This invention relates to a method and composition for regulating (increasing and decreasing) the level of glycine in the brain and in the spinal cord.
Prior to the present invention, it was thought that glycine was formed in vivo, in the mammalian central nervous system, from serine by the removal of a hydroxyl group. It had also been proposed that glycine could be produced in vivo by the aldol cleavage of threonine to yield glycine and acetaldehyde, Meltzer et al, J. Biol. Chem., 107, pp 461-474 (1952). In order to test this hypothesis, experiments were conducted with chicks that were fed a diet containing L-threonine to determine the effect of L-threonine on glycine formation in vivo. As reported by D'Me lo at Nutr. Metabol., 15, pp 357-363 (1973), L-threonine was found to have no appreciable influence on plasma glycine levels. Accordingly, it was concluded that threonine is not readily degraded to glycine and that it cannot act as a precursor of glycine.
Glycine is known to be an inhibitory neurotransmitter in the brain and, especially, the spinal cord. Prior to the present invention, there are no drugs or other treatments for increasing the amount of glycine present in synapses. It is known that conditions or treatments that decrease neuronal glycine levels such as spinal cord lesions or that block glycine's interactions with its receptors such as the poison strychnine cause spasticity and hyper-reflexia. Brain glycine levels also are depressed when animals receive anti-psychotic drugs chronically and glycine-mediated neurotransmission may be involved in the actions of some tranquillizing drugs (like the benzodiazopines).
It would be highly desirable to provide a means for increasing or decreasing the amounts of glycine in the brain and in the spinal cord. Furthermore, it would be desirable to provide such a means which is biochemically specific and which lacks the undesirable side effects of anti-spasticity drugs (such as mephenesin analogs, that cause jaundice, nystagmus, and nausea; or dantrolene, which produces weakness). Such a means would be useful in conditions associated with spasticity such as backache or muscle strain. In addition, such means could be utilized in conjunction with anti-psychotic drugs that have the undesirable side effect of lowering brain glycine levels, or with tranquillizing drugs that act as glycine receptors.